The invention relates to compositions and methods for treating hematological malignancies, including multiple myeloma.
Multiple myeloma is a cancer of plasma cells that accumulate in the bone marrow. Multiple myeloma remains uncurable despite recent advances in understanding its molecular pathogenesis and the development of promising new therapies.
The canonical Wnt pathway is constitutively active in multiple myeloma and promotes tumor cell proliferation and disease progression; however, mutations in Wnt pathway members APC, Axin or β-catenin have not been reported. Instead, the mechanism of pathologic Wnt signaling in multiple myeloma has been linked to post-transcriptional regulation of β-catenin and/or increased levels of BCL9, implicating the β-catenin co-factor as a bona fide oncogene.
The Wnt/β-catenin signaling pathway is implicated in the pathogenesis of a broad range of cancers and has emerged as a promising target for therapy. Loss-of-function mutations in APC and Axin, as well as activating mutations in β-catenin itself, facilitate β-catenin nuclear translocation and drive oncogenic Wnt transcription.